Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium

Kin, Takusho; Horino, Satoshi; Moon, Jihoon; Tsuda, Momoka; Gröger, Harald; Akai, Shuji; Kanomata, Kyohei

doi:https://doi.org/10.1039/D4GC06535B

Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium

Kin, Takusho; Horino, Satoshi; Moon, Jihoon et al.

Green Chemistry, 2025

アクセス数:11件（2025-08-17 17:16 集計）

固定URL: https://hdl.handle.net/11094/102428

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タイトル	Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium
著者	著者名 Kin, Takusho
	著者名 Horino, Satoshi
	著者名 Moon, Jihoon
	著者名 Tsuda, Momoka
	著者名 Gröger, Harald
	NRID 1000060192457 1000060192457 ORCID 0000-0001-9149-8745 0000-0001-9149-8745 researchmap permalink shuji_akai shuji_akai Scopus Author ID 7006001526 7006001526 著者名 Akai, Shuji
	NRID 1000030880447 1000030880447 ORCID 0000-0002-2251-4665 0000-0002-2251-4665 researchmap permalink kyohei_kanomata kyohei_kanomata Scopus Author ID 39861733600 39861733600 著者名 Kanomata, Kyohei
内容	Reproduced from Green Chem., 2025 with permission from the Royal Society of Chemistry.
抄録	Chemoenzymatic dynamic kinetic resolution (DKR) provides a promising green approach for synthesizing optically active alcohols and their derivatives, which serve as widely used key intermediates in the fine chemical industry. While lipase-catalysed DKR of secondary alcohols has been extensively studied, the DKR of tertiary alcohols remains a significant challenge, even in advanced organic synthesis. This is mainly because tert-alcohols are poorly reactive to esterification owing to steric hindrance and are prone to dehydrative side reactions. In this study, the combined use of a lipase and the strong Brønsted acid H₂SO₄ enabled the efficient DKR of racemic tert-alcohols to produce the corresponding esters with high enantiomeric excess (95–99% ee) in 56–91% isolated yields. In this DKR system, lipase-catalysed kinetic resolution in the oil phase and H₂SO₄-catalysed racemization of the unreacted enantiomer of the alcohol in the aqueous phase proceeded concurrently in one reactor. This simultaneous use of the inherently incompatible combination of a lipase and a strong Brønsted acid was realized by integrating phase separation via a hydrophobic polydimethylsiloxane membrane and a recycling flow reaction system. In addition, side reactions were completely suppressed by conducting the racemization reaction in the aqueous phase, enabling the application of this DKR methodology to a range of tert-alcohols, thus demonstrating, for the first time, a generally applicable DKR system for tert-alcohols.
出版者	Royal Society of Chemistry (RSC)
収録物名	Green Chemistry
刊行年月	2025-07-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102428
PISSN	14639262
eISSN	14639270
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1039/D4GC06535B
アクセス権	embargoed access
権利情報	Reproduced from Green Chem., 2025 with permission from the Royal Society of Chemistry.
権利情報	The full-text file will be made open to the public on 10 July 2026 in accordance with the publisher's policy.
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Green Chemistry. 2025
DC.title	Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium
DC.creator	Kin, Takusho
	Horino, Satoshi
	Moon, Jihoon
	Tsuda, Momoka
	Gröger, Harald
	Akai, Shuji
	Kanomata, Kyohei
DC.publisher	Royal Society of Chemistry (RSC)
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-10
DC.identifier	https://doi.org/10.1039/D4GC06535B
DC.description	Reproduced from Green Chem., 2025 with permission from the Royal Society of Chemistry.
DCTERMS.abstract	Chemoenzymatic dynamic kinetic resolution (DKR) provides a promising green approach for synthesizing optically active alcohols and their derivatives, which serve as widely used key intermediates in the fine chemical industry. While lipase-catalysed DKR of secondary alcohols has been extensively studied, the DKR of tertiary alcohols remains a significant challenge, even in advanced organic synthesis. This is mainly because tert-alcohols are poorly reactive to esterification owing to steric hindrance and are prone to dehydrative side reactions. In this study, the combined use of a lipase and the strong Brønsted acid H₂SO₄ enabled the efficient DKR of racemic tert-alcohols to produce the corresponding esters with high enantiomeric excess (95–99% ee) in 56–91% isolated yields. In this DKR system, lipase-catalysed kinetic resolution in the oil phase and H₂SO₄-catalysed racemization of the unreacted enantiomer of the alcohol in the aqueous phase proceeded concurrently in one reactor. This simultaneous use of the inherently incompatible combination of a lipase and a strong Brønsted acid was realized by integrating phase separation via a hydrophobic polydimethylsiloxane membrane and a recycling flow reaction system. In addition, side reactions were completely suppressed by conducting the racemization reaction in the aqueous phase, enabling the application of this DKR methodology to a range of tert-alcohols, thus demonstrating, for the first time, a generally applicable DKR system for tert-alcohols.
DC.rights	Reproduced from Green Chem., 2025 with permission from the Royal Society of Chemistry.
DC.rights	The full-text file will be made open to the public on 10 July 2026 in accordance with the publisher's policy.
DC.format	102428
citation_title	Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium
citation_author	Kin, Takusho
	Horino, Satoshi
	Moon, Jihoon
	Tsuda, Momoka
	Gröger, Harald
	Akai, Shuji
	Kanomata, Kyohei
citation_publisher	Royal Society of Chemistry (RSC)
citation_language	英語
citation_date	2025-07-10
citation_journal_title	Green Chemistry
citation_doi	https://doi.org/10.1039/D4GC06535B
citation_public_url	https://hdl.handle.net/11094/102428

Dynamic kinetic resolution of tert-alcohols via combination of a lipase/Brønsted acid in a biphasic reaction medium

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